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A New Approach for Deciphering Complex Immune Responses

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The response to infection is highly variable from one individual to another. The Milieu Intérieur consortium, coordinated by Prof. Matthew Albert (Immunobiology of dendritic cells Unit, Institut Pasteur / Inserm) and Dr Lluis Quintana-Murci (Human Evolutionary Genetics Unit, Institut Pasteur / CNRS) seek to establish the parameters that characterize the immune system of healthy individuals and its natural variability. In a study just published (August 25th) in Cell Reports, coauthored by Magnus Fontes (Centre for Mathematical Sciences, Lund University and International Group for Data Analysis, Institut Pasteur) and one of Qlucore’s founders, the researchers describe a new approach for analyzing the inflammatory response at the gene expression level in blood samples from healthy individuals, which reproduces the conditions of in-vivo stimulation. The striking result from this study is that the immune response to complex stimuli such as bacteria, viruses, and fungi could be defined and distinguished based on a small number of genes that were induced by 4 key immune proteins or cytokines. In particular as few as fourty-four genes, that were identified by machine learning techniques, could explain the variance present within such diverse immune responses. At a time of high-throughput sequencing approaches which create huge challenges for data analysis and medical applications, this study suggests that simplified approaches if properly targeted may provide more effective solutions with easier clinical translation. In addition, the study highlights that the utilization of highly standardized techniques for all steps including sample collection, sample preparation, and data analysis results in the generation of higher quality and more informative data. “We are excited by the results of this study which demonstrated that a relatively small subset of identified genes could explain the variability in responses to different complex immune stimuli” said Dr Darragh Duffy, immunologist and manager of the Milieu Interieur consortium at Institut Pasteur, Paris.

In support of the published article, reference values are providied for each immune stimuli which reflects the natural variation of immune responses in humans. An online application was also released which provides an opportunity for the scientific community to exploit these data and to explore which genes are induced by a variety of immune stimuli. This newly established approach is now being applied to the 1000 healthy donors within the Milieu Intérieur cohort, which will enable the dissection of how age, gender, environment, lifestyle, and genetics contribute to variable immune responses. This is a first necessary step on the path towards precision medicine approaches.

Several of the data analyses in this study were carried out using Qlucore Omics Explorer. Most of the up-stream analyses in the study can quickly be reproduced using Qlucore Omics Explorer, directly downloading the data from Gene Expression Omnibus (GEO). This work is one example of how Qlucore Omics Explorer is used by scientists, who can browse an extensive list of links to many hundreds [more than 300] scientific articles from peer-reviewed journals written by Qlucore clients.